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    Poster Networking

    Vascular Biology

    Poster Networking Session

    PB1430 - Vascular injury derived exosomes are involved in break in tolerance to vascular autoantigens

    Tuesday, June 27, 2023
    18:30 – 19:30 ET
    Room: Exhibition
    Background: Apoptotic exosomes (ApoExo) are vascular injury derived extracellular vesicles (EVs) released by apoptotic endothelial cells (EC). Their comprehensive characterization showed distinct size, protein, ARN profile and enzymatic activity from classical apoptotic bodies. We have shown that ApoExo accelerated vascular rejection in association with circulating anti-LG3/perlecan autoantibodies (AutoAb). We have also demonstrated that anti-LG3 antibodies can trigger microvascular rarefaction in ischemic kidneys and in lupus prone mice.

    Aims: We hypothesize that ApoExo stimulate specific B cells that exist in the normal immune repertoire to secrete AutoAb and that pro-inflammatory condition prevalent in the context of organ transplantation and autoimmune diseases can amplify this response.

    Methods: B cells from spleen or peritoneal cavity (pc) were isolated from C57Bl/6 mice. After in vitro stimulation with Toll-Like-Receptor (TLR) agonists, anti-LG3 levels were assessed in supernatants by ELISA. Serum-free medium conditioned by apoptotic murine EC from C57Bl/6 mice is fractionated based on sequential centrifugations up to 200 000g and ApoExo were isolated and quantified. C57Bl/6 mice were infused with ApoExo or vehicle every second day for 3 weeks. At sacrifice, splenocytes and pc lymphocytes were analyzed as above and by flow cytometry. Circulating AutoAb were quantified by ELISA /microarray and cytokine levels were evaluated by multiplex.

    Results: B cells specific to LG3 were found in the pc of C57Bl/6 mice and produced anti-LG3 AutoAb when stimulated with TLR 1/2, 4, 7 and 9 agonists. Interestingly, these cells disappeared from the pc of mice infused with ApoExo. ApoExo infusion also triggered circulating IL-23/IL-17 autoimmune axis, increased splenic Germinal center B cell, increased total circulating IgG and significant production of classical AutoAb such as anti-dsDNA, anti-SSA-B anti-Sm/nRNPand anti-LG3.

    Conclusion(s): These observations suggest a specific role for vascular injury derived EVs ApoExo in modulating the production of AutoAb which, in turn, trigger microvascular involution of importance in autoimmune diseases and transplant rejection.